Certain members of the human population suffer from mental disorders known as psychoses, and such individuals exhibit abnormal perceptual and behavioral characteristics. Attempts have been made to develop a biochemical explanation for psychoses, and these attempts have focussed on the possible role of certain substances found in the brain and known as biogenic amines (e.g. dopamine). In particular, the possible importance of chemical imbalances among these biogenic amines has been studied.
On the other hand, it has been known for several years that in some cases it is possible to alleviate the symptoms of psychotic disorders by the administration of certain chemical substances known as antipsychotic, ataractic or neuroleptic agents. Both naturally-occurring substances and chemically synthesized agents have been used in this regard. For example, extracts from the shrub Rauwolfia serpentina have long been used in Hindu medicine, and a constituent of these extracts, the alkaloid reserpine, has been shown to have antipsychotic properties. Two, well-known classes of synthetic compounds which have found use in clinical medicine for the drug therapy of psychoses are phenothiazines, e.g. chlorpromazine, and butyrophenones, e.g. haloperidol.
However, no single compound has been found which is ideally suited for the treatment of all psychoses; consequently, the search for new antipsychotic agents continues.
Accordingly, it is an object of the present invention to provide a new series of chemical compounds which are of value in the treatment of psychoses. More particularly, these new chemical compounds are piperidine derivatives, having a phenylalkyl group at the 1-position and a 3-hydroxyphenyl group at the 3-position, and optionally having further substituents.
Julia et al., Bull. Soc. Chim. France, 3, 1000 (1968) have reported the preparation of a series of 3-phenylpiperidines, including 1-(2-phenylethyl)-3-(3-hydroxyphenyl)piperidine, and the latter compound has been shown to have dopamine-autoreceptor stimulating activity (Hacksell et al., J. Med. Chem., 24, 1475 [1981]). Published PCT patent application No. 81/01552 discloses a series of 1-substituted-3-(3-hydroxyphenyl)-piperidines as dopamine-autoreceptor agonists.